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TISSUE-SPECIFIC STEM CELLS

Sustained Exposure to Nicotine Leads to Extramedullary Hematopoiesis in the Spleen

Division of Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego, California, USA

Key Words. Nicotine • Bone marrow • Spleen • Hematopoiesis stem progenitor cells • Extramedullary hematopoiesis

Correspondence: P. Sriramarao, Ph.D., Division of Vascular Biology, La Jolla Institute for Molecular Medicine, 4570 Executive Drive, San Diego, California 92121, USA. Telephone: 858-587-8788, ext. 101; Fax: 858-587-6742; e-mail: rao{at}ljimm.org

Received September 13, 2005; accepted for publication June 15, 2006.
First published online in STEM CELLS EXPRESS   July 6, 2006.



The effect of sustained exposure to nicotine, a major constituent of cigarette smoke, on hematopoiesis in the bone marrow (BM) and spleen was evaluated in a murine model. BALB/c mice were exposed to nicotine subcutaneously using 21-day slow-release pellets. Exposure to nicotine had no effect on the proliferation of long-term BM cultures or on their ability to form colonies. However, there was a significant decrease in the generation of lineage-specific progenitor cells, specifically eosinophil (colony-forming unit [CFU]-Eos) progenitors, in the BM of nicotine-exposed mice compared with control mice. Surprisingly, sustained exposure of mice to nicotine was found to induce significant hematopoiesis in the spleen. There was a significant increase in total colony formation as well as eosinophil-, granulocyte-macrophage-, and B-lymphocyte-specific progenitors (CFU-Eos, CFU-GM, and CFU-B, respectively) in nicotine-exposed mice but not in control mice. Sustained exposure to nicotine was associated with significant inhibition of rolling and migration of enriched hematopoietic stem/progenitor cells (HSPCs) across BM endothelial cells (BMECs) in vitro as well as decreased expression of ß2 integrin on the surface of these cells. Although sustained exposure to nicotine has only a modest effect on BM hematopoiesis, our studies indicate that it significantly induces extramedullary hematopoiesis in the spleen. Decreased interaction of nicotine-exposed HSPCs with BMECs (i.e., rolling and migration) may result in altered BM homing of these cells, leading to their seeding and proliferation at extramedullary sites such as the spleen.